How to Understand a Revolution: Guts, Lungs, and Bronchiectasis
Authors: Callie M. Drohan, Philip L. Molyneaux, Robert P. Dickson
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Guts, Lungs, and BronchiectasisSuppose a scholar seeks to understand the American Revolutionary War: its causes, consequences, and what lessons we may learn from it.They begin by reading biographies of key participants but soon realize that the scope of these books is too narrow.Broadening the scope to study demography (e.g., census reports, immigration records) helps them understand not merely the leaders of the revolution but also the people they led.However, even this isn't enough to understand the colonists' activities, so the scope is broadened further to interactions: in governance (political science), in the marketplace (economics), and in culture (sociology).Finally, our historian realizes that they cannot understand the events of Boston, Philadelphia, and Yorktown without also studying England: the leaders, people, and interactions that influenced a revolution from across an ocean.This sequence-the broadening of one's scope of study to understand a complex historical phenomenon-provides us with a useful analogy for understanding another revolution: the introduction of culture-independent microbiology to our study of respiratory disease (1) (Table 1).For a century, the study of microbiota in the lungs relied on "biographies" of individual species: culture-based interrogation of prominent pathogens, studied by means of culturedependent bacteriology and mycology.In the past decade, the use of microbiome techniques (amplicon sequencing, metagenomics) has revealed the complex "demography" of respiratory microbiota: diverse, dynamic populations of microbiota detected in healthy and diseased airways.However, with rare exceptions (2), the field has not reached the "interactions" scale of inquiry.We know little about the complex networks that exist between respiratory microbiota, the host, and mediators of disease pathogenesis.Furthermore, studies of the microbiome's role in lung disease have been anatomically compartmentalized, sampling either respiratory microbiota or gut microbiota, but never both.We've been trying to understand a revolution with an incomplete toolkit, looking through a narrow lens.In this issue of the Journal, Narayana and colleagues (pp.908-920) move the field forward by broadening our scope of inquiry.Seeking to better understand the microbiome's role in bronchiectasis, they studied a cohort of 57 adult patients with bronchiectasis (3).Although modest in size, the cohort was extensively and exhaustively characterized, both anatomically (both respiratory and gut specimens) and taxonomically (they studied both bacteria and fungi).This integrated strategy of crosscompartmental sampling and cross-kingdom sequencing is novel and enabled them to perform interactome analyses that incorporated both gut and lung communities, both bacterial and fungal.Their core finding was that these patients with bronchiectasis cluster into two distinct subgroups, identified through their network analysis: a high gut-lung interaction group (dominated by lung